There is a growing need for a home diagnostic system for monitoring various personal physiological conditions especially for the prediction of ovulation for women. A reliable method of predicting ovulation can determine a woman s fertility period for pregnancy as well as for birth control. A convenient oral device such as an electrical toothbrush having a built-in ovulation-monitoring capability is desirable for checking a woman's fertility condition on a daily basis.
(1) Field of the Invention
The present invention relates to ovulation-monitoring oral devices and electrical toothbrushes by detecting the crystallization and ferning pattern of dried saliva samples.
(2) Related Art
It is known that a woman's menstrual cycle, in general, lasts from 27 to 30 days, while menstruation lasts from 3 to 7 days in the cycle. In each cycle a woman can conceive only during about a three to six day window. As a woman's fertile period lasts about six days and ends on the day of ovulation a fertility test based upon detection of ovulation on the ovulation day is too late to be useful in determining the fertility time for planning. For advanced prediction a urine test on the concentration of luteinizing hormone (LH) can detect ovulation 1-2 days ahead of time but the test is not sufficient to detect the entire fertile period of three to six days.
There are many methods for predicting a woman's ovulation. It is known in the art to measure a woman's body temperature which increases with estrogen's rise to detect fertile times. It has been demonstrated that shortly after menstruation begins the body temperature decreases until ovulation starts, after that the temperature increases. During the menstruation period, the vaginal secretions also becomes increasingly viscous and to peak at the time of maximum fertility. These body temperature and viscosity measurements methods, however, are not reliable in determining fertile periods. Other ovulation prediction methods include a blood test and an urine test for detecting a surge in estrogen-related hormone. These tests can determine whether the woman is at ovulation instead of providing advanced signal of impending ovulation.
Saliva is a complex body fluid containing several different electrolytes including salts of sodium, potassium chloride and non-electrolyte components including several proteins, enzymes, and immunoglobulins. U.S. Pat. No. 4,770,186 by Regas et al. uses a sensor probe for measuring the electrical resistance of a saliva. Daily measurements are made beginning not more than five days following the beginning of menstruation. The onset of ovulation is determined as a function of a peak electrical resistance measurement following the onset of menstruation. A Stage A peak of salivary electrical resistance (SER) occurs approximately six days, plus or minus one day, prior to ovulation. After a sharp dip following the Stage A peak, Stage B peak occurs approximately 2 days before ovulation, plus or minus one day and it is a sign of imminent ovulation. Although the trend of changing electrical resistance of these electrolytes in saliva can be used to predict the impending ovulation, the appearance of multiple peaks prior to ovulation is too complicated to make a reliable judgement. Furthermore, the signal level of the electrical resistance is generally too weak to enable an accurate prediction.
Specifically, several patents in prior art describe various methods for collecting and diagnosing the contents of saliva for the prediction of ovulation. U.S. Pat. No. 3,968,011 by Manautou et al. shows the use of the optical density curves of saliva samples to indicate pregnancy. Such curves have a first peak and a smaller second peak in daily measurements; however, the second peak is eliminated when pregnancy occurs. In application, a paper test strip impregnated with a peroxidase and guaiac shows a color change when wet with saliva during the fertile period. The change is caused by the presence of peroxide in the saliva. The test strip is costly and may not be reused. U.S. Pat. No. 4,385,125 by Preti et al. monitors saliva for the concentration of certain long-chain alcohols, particularly dodecanol, for detecting ovulation. The dodecanol content of saliva remains at a relatively constant level throughout the menstrual cycle, but exhibits a single peak at the time of ovulation. Because the method requires the use of an incubated saliva sample, it is more suitable for laboratory tests than home use. Also the fact that the dodecanol level exhibits a single peak or spike precisely corresponding to ovulation does not enable prediction of a fertile period ahead of ovulation necessary for planning. U.S. Pat. No. 5,914,271 by Law et al. discloses that a saliva's calcium and magnesium concentration drops in the three to five day period immediately prior to ovulation. It provides methods of monitoring the calcium and magnesium concentration. All the methods include using a reagent composition such as calcium or magnesium sensitive dye or pigments which undergoes a visible change in the presence of a clinically significant threshold concentration of the ion. However, the use of reagent for a test stripe, ion-selective electrodes, or a handheld reflectometer for detecting different color shades is inconvenient for regular home testing.
Several commercially available hand held devices predict ovulation based on a measured peak in electrical resistance corresponding to sodium and potassium electrolyte levels which are reflective of hormone changes that occur several days before ovulation. The measured data on the changes of electrolytes in saliva may be inconsistent since an oral sensor probe is placed on the tongue where the thickness of the saliva layer may vary. While there are disadvantages associated with all of the above methods, each method demonstrates the feasibility of using an optical sensor or a conductivity sensor for measuring signals derived from a saliva sample to predict a fertile period or ovulation.
Another method for determining the ovulation is by visual examination of a woman's dried saliva. The method is based on observations of crystallized salt pattern in a dried saliva, which is referred as ferning pattern. The physical basis of ferning pattern is not well known. Some research results correlate the crystallization pattern with increases in the chloride content, changes in ionic strength and/or the content of sodium or potassium in the saliva. Research results mentioned in U.S. Pat. No. 4,815,835 by Corona indicates that saliva crystallization appears when the blood folliculin level has reached a certain height that coincides with the third or fourth day before ovulation. The crystallization pattern is visible under 100-fold magnification of a saliva sample on a slide. The crystallization lasts until 3 or 4 days after ovulation, when the presence of lutein inhibits the crystallization. At fertile times, microscopic viewing of dried saliva reveals a structure of salt distribution pattern that starts to form chains. This method of examination of saliva offers a reliable way to determine fertility.
U.S. Pat. No. 5,572,370 by Cho describes an apparatus for determining the fertile periods of women based on laboratory observations of crystallized saliva under high magnification. When a woman is most fertile, the saliva dries in fern-like patterns and during non-fertile periods the saliva pattern is random and generally appears as unconnected dots. When a combination of dots and fern-like patterns appear, it indicates that the woman is in a transitional period that a conception is possible but not highly likely. The patent states that laboratory tests have shown the fern-like structures appearing approximately three to four days prior to ovulation and ending two to three days after ovulation. However, the described method relies on the experience of visual observations and comparisons with standard patterns for determination of the fertile and non-fertile conditions of the woman being tested, therefore, it is subject to inaccuracies. Also described in U.S. Pat. No. 5,639,424 by Rausnitz is a portable fertility tester for viewing the ferning pattern of a dried saliva sample. The tester has a circular disc with transparent regions indexed to each of the days of the menstrual cycle for storing the saliva patterns for viewing. An ocular is provided with a magnifying lens for examining the appearance of a woman's saliva sample placed on the tester. After drying, a fern-like pattern indicates the woman at a fertile time or a structureless dotted pattern indicates non-fertile. The ovulation tester was approved by FDA in January of 2002 (The Associate Press news article on Jan. 19, 2002). The device, however, depends solely on qualitative viewing of multiple stored saliva samples for determining the fertility condition and no quantitative trend is established for more accurate prediction of ovulation.
Instead of qualitative visual observations of crystalline patterns, U.S. Pat. No. 6,159,159 by Canter et al. describes an approach of ovulation monitoring by quantitatively determining the degree of ferning on the basis of diffraction of light by a crystallized saliva sample. A laser light is directed onto a targeted location on a dried sample that reflects scattered light onto a two-dimensional photo diode array. The photo diode array inputs the light intensity profile to a microprocessor. The microprocessor has a programmed algorithm that calculates a local ferning index representing a characteristic structure in the diffraction pattern of the targeted location. By this means, a number of locations are selected for obtaining a summary ferning index that represents the degree of ferning of the whole saliva sample. The approach uses a threshold value for determining the fertility of the saliva sample. The accuracy of this method, however, depends on selected measurement locations, which may not represent the whole imaged area of a dried saliva.
The analysis of a ferning pattern requires image processing of a captured image of a dried saliva sample by a digital camera. The analysis involves the framing of line segments appearing in the imaged area of a dried saliva sample. A method of framing a test image for comparing with a template is described in U.S. application Ser. No. 10/059477 by Kuo et al. for signature verification and character recognition. With the input of the stored pixel values, an OCR program proceeds to frame a first test character by scanning from the left end of the field toward the right end of the field. The first test character frame increases in size in the direction where the coverage area of dark pixels increases. This operation is repeated until the final frame is reached, by which further increase of frame size in any direction does not increase the coverage area of dark pixels. The template character that presents the best match is identified as the character for the test character. The methodology as described is for determining the best match of images, however, it is not applicable for characterizing the structure of a crystallization pattern of a dried saliva sample.
For daily home measurement of the Ferning pattern of a dried and crystallized sample, a convenient and well defined saliva collection method needs to be developed. The prior art has disclosed various means for collecting saliva samples. U.S. Pat. No. 4,834,110 by Richard describes a suction cup for collecting a saliva sample. Suction is applied to a person's cheek around the parotid salivary duct and a pulsing pressure or electrical stimulation is applied to promote the flow of saliva to a collector vessel. The device is for one-time use in laboratory testing and it does not control the sample size for testing. Another device using a collecting cup for monitoring saliva is disclosed in U.S. Pat. No. 6,061,586 by Kuperman et al. The device includes a sample kit and an electrode assembly for immersion within a patient's saliva. The sample kit is comprised of a syringe-like element with a piston and a sponge member for absorbing the saliva which is to be compressed by the piston into the collecting cup. Disadvantages of the method are potential contamination of saliva by the sponge and the mechanical handling of the saliva that may impact the alignment of salts pattern.
A convenient saliva collection and testing method is disclosed in U.S. Pat. No. 6,623,698 by Kuo. It describes the use of a biosensor electrical toothbrush that has a drive head having a test channel and a renewable biosensor system within the test channel for performing routine saliva tests. The drive head stimulates saliva production and collects a fixed quantity of saliva in the test channel where measurement signals are produced by sensors. The signals are transmitted to a microprocessor in the handle for storage and diagnostic analysis of the saliva sample. The brush handle also includes a display means, a battery, a motor and a reservoir for storing a reagent which is supplied in controlled quantities to the channel during saliva testing. The biosensor electrical toothbrush as described, however, is for measuring properties of a liquid saliva. It is not for capturing an image of a dried saliva sample for detecting crystallization.
In summary, there have been a significant number of patents which utilize saliva samples to predict a woman's ovulation. While various patents in the prior art describe methods for predicting ovulation, none is capable of performing the stimulation and collection of saliva and testing the saliva sample in an all-in-one handheld device for economic, efficient and convenient repeated regular uses at home.
It is therefore an object of this invention to provide a portable handheld diagnostic oral device which stimulates saliva production and collects saliva samples in a test channel. It is another object of the invention to test dried saliva samples of a user for the purpose of monitoring the Ferning crystallization pattern on a daily basis. It is a further object of the invention to provide a portable hand held diagnostic device which has a toothbrush component.